Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001380460 | SCV001578542 | pathogenic | Alstrom syndrome | 2024-01-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp972Valfs*8) in the ALMS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALMS1 are known to be pathogenic (PMID: 17594715). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1068792). For these reasons, this variant has been classified as Pathogenic. |
Victorian Clinical Genetics Services, |
RCV001380460 | SCV002768851 | pathogenic | Alstrom syndrome | 2020-05-21 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v0.6.1, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease for this gene. 0106 - This gene is known to be associated with autosomal recessive disease. 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein. 0301 - Variant is absent from gnomAD. 0507 - Identified variant type is not compatible with in-silico predictions of pathogenicity. 0701 - Comparable variant in relevant codon/region has very strong previous evidence for pathogenicity. 0807 - Variant has not previously been reported in a clinical context. 0905 - No published segregation evidence has been identified for this variant. 1007 - No published functional evidence has been identified for this variant. 1201 - Heterozygous variant detected in trans with a second (likely) pathogenic heterozygous variant in a recessive disease. 1206 - Variant is paternally inherited. |